53BP1 Regulates DSB Repair Using Rif1 to Control 5′ End Resection

  title={53BP1 Regulates DSB Repair Using Rif1 to Control 5′ End Resection},
  author={Michal Zimmermann and Francisca Lottersberger and Sara C. B. Buonomo and Agnel Sfeir and Titia de Lange},
  pages={700 - 704}
Fixing Broken DNA Some physiological processes, such as immunoglobulin class switching and telomere attrition, result in double-stranded DNA breaks. The DNA damage repair protein, 53BP1, prevents nucleolytic processing of these breaks, but the proteins it partners with to do this are unknown (see the Perspective by Lukas and Lukas). Di Virgilio et al. (p. 711, published online 10 January), using mass spectroscopy–based methods, and Zimmermann et al. (p. 700, published online 10 January), using… 
To trim or not to trim: Progression and control of DSB end resection
The emerging view suggests that besides endo/exonucleases and helicases activities required for end resection, molecular barrier factors are specifically loaded in the proximity of the break, where they physically or functionally limit DNA degradation, preventing excessive accumulation of ssDNA, which could be threatening for cell survival.
Double-strand break repair: 53BP1 comes into focus
A model is emerging in which 53BP1 recruitment requires the direct recognition of a DSB-specific histone code and its influence on pathway choice is mediated by mutual antagonism with breast cancer 1 (BRCA1).
53BP1: pro choice in DNA repair.
PHF11 promotes DSB resection, ATR signaling, and HR.
It is reported that PHF11 (plant homeodomain finger 11) encodes a previously unknown DDR factor involved in 5' end resection, ATR signaling, and HR.
FAM35A co-operates with REV7 to coordinate DNA double-strand break repair pathway choice
A previously undescribed factor, FAM35A/SHDL2, is established as a novel effector of REV7 in controlling the decision-making process during DSB repair and NHEJ-mediated DNA repair is established.
DNA repair pathway choice—a PTIP of the hat to 53BP1
These findings suggest that 53BP1 and BRCA1 battle each other to influence DSB repair pathway choice, and are especially germane to those interested in the genesis of breast and ovarian cancer caused by a defective BrcA1 protein, which is crucial for D SB repair by HR.
Role of 53BP1 in the Regulation of DNA Double-Strand Break Repair Pathway Choice
Recent advances in understanding the role of 53BP1 in regulating DNA DSBs repair pathway choice, variable diversity joining [V(D)J] recombination and class-switch recombination (CSR) are summarized.


53BP1 promotes non-homologous end joining of telomeres by increasing chromatin mobility
It is proposed that the binding of 53BP1 near DNA breaks changes the dynamic behaviour of the local chromatin, thereby facilitating NHEJ repair reactions that involve distant sites, including joining of dysfunctional telomeres and AID-induced breaks in immunoglobulin class-switch recombination.
Shelterin-Like Proteins and Yku Inhibit Nucleolytic Processing of Saccharomyces cerevisiae Telomeres
The role of key telomeric proteins in protecting budding yeast telomeres from degradation is investigated and it is shown that the Saccharomyces cerevisiae shelterin-like proteins Rif1, Rif2, and Rap1 inhibit nucleolytic processing at both de novo and native telomereres during G1 and G2 cell cycle phases.
Human CtIP promotes DNA end resection
These findings establish evolutionarily conserved roles for CtIP-like proteins in controlling DSB resection, checkpoint signalling and homologous recombination.
Removal of Shelterin Reveals the Telomere End-Protection Problem
To define the end-protection problem, the whole shelterin complex is removed from mouse telomeres through conditional deletion of TRF1 and TRF2 in nonhomologous end-joining (NHEJ) deficient cells, and two DNA damage response pathways not previously observed upon deletion of individual shelterin proteins are revealed.
DNA processing is not required for ATM-mediated telomere damage response after TRF2 deletion
Activation of the ATM kinase pathway at chromosome ends does not require overhang degradation or other overt DNA processing, and telomere structure after conditional deletion of mouse TRF2, the protective factor at telomeres is studied.
53BP1 facilitates long-range DNA end-joining during V(D)J recombination
A previously unrecognized defect in the joining phase of V(D)J recombination in 53BP1-deficient lymphocytes is reported that is distinct from that found in classical non-homologous-end-joining-, H2ax-, Mdc1- and Atm- deficient mice, suggesting a more general role for 53BP 1 in maintaining genomic stability during long-range joining of DNA breaks.
DNA Damage Foci at Dysfunctional Telomeres